New Form Of Gene Therapy Holds Promise For The Future

October 23, 1997

DALLAS - October 23, 1997 - Scientists at UT Southwestern Medical Center at Dallas are one step closer to producing a "drug" that is internally regulated and activated only when needed.

They have developed a system in mice in which the level of a genetically engineered protein responds to inflammatory signals produced by the mice themselves. This method of gene therapy, described in the October issue of Nature Biotechnology, may have great potential for treating chronic relapsing and remitting inflammatory diseases, such as rheumatoid arthritis, and organ transplant rejection.

"Our long-range goal is to give patients the right amount of an anti-inflammatory protein, at the right time and in the right place, to control damaging inflammation by introducing the gene for the protein and allowing the body's own signals to control its production," said Dr. Robert Munford, professor of internal medicine and microbiology and holder of the Jan and Henri Bromberg Chair in Internal Medicine.

According to Munford, who worked with Dr. Alan Varley, a research fellow in internal medicine, and research technician Steven Geiszler, "There are lots of hurdles to overcome, but Varley and Geiszler seem to have jumped the first one, showing that recombinant genes can actually be regulated in animals in response to inflammation."

The investigators used a "reporter" gene - a gene that encodes an easily measured protein - to test the ability of a mouse's immune response to turn on that gene. The reporter gene they used was firefly luciferase, an enzyme that causes light emission and can be measured easily with a luminometer. In the laboratory, they inserted the luciferase gene into a genetically altered virus that could not reproduce. To stimulate and control the production of luciferase, the researchers inserted specific short pieces of deoxyribonucleic acid (DNA) in front of the luciferase gene. These short DNA elements respond to internal signals by turning genes on and off.

The trick was to find the right combination of DNA elements to dramatically enhance production of luciferase in response to an inflammatory reaction.

The successful combination consisted of three elements ? one from the mouse and two from a virus ? that worked in concert and greatly amplified the production of luciferase when the proper signals (in this case, an inflammatory reaction) were received.

The luciferase gene preceded by the three short pieces of DNA was genetically inserted into the viral molecule and injected into mice. Researchers then induced two different types of inflammatory responses. They determined how successful their combination of elements was by measuring the amount of luciferase produced in the mouse's liver, spleen, lung, heart and kidney.

If a gene for an anti-inflammatory protein is used in place of the luciferase gene, this type of gene therapy, in theory, would activate that protein in response to the body's own inflammatory signals.

"The production level of the anti-inflammatory protein should reflect the intensity and duration of the inflammatory condition," said Munford. "If the gene can be delivered to a specific site, such as an inflamed joint or an organ about to be transplanted into a recipient, it may be possible to provide effective anti-inflammatory treatment while avoiding systemic immunosuppression with its risk of infection."

Dr. Richard Gaynor, professor of internal medicine and microbiology, and holder of the Andrea L. Simmons Distinguished Chair in Cancer Virology, also collaborated in the studies.
-end-



This news release is available on our World Wide Web home page at http://www.swmed.edu/news/newspubs.htm/

UT Southwestern Medical Center

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.